ASICS: Authenticated Key Exchange Security Incorporating Certification Systems

Most security models for authenticated key exchange (AKE) do not explicitly model the associated certification system, which includes the certification authority and its behaviour. However, there are several well-known and realistic attacks on AKE protocols which exploit various forms of malicious key registration and which therefore lie outside the scope of these models. We provide the first systematic analysis of AKE security incorporating certification systems. We define a family of security models that, in addition to allowing different sets of standard AKE adversary queries, also permit the adversary to register arbitrary bitstrings as keys. For this model family, we prove generic results that enable the design and verification of protocols that achieve security even if some keys have been produced maliciously. Our approach is applicable to a wide range of models and protocols; as a concrete illustration of its power, we apply it to the CMQV protocol in the natural strengthening of the eCK model to the ASICS setting

Efficient One-round Key Exchange in the Standard Model

We consider one-round identity-based key exchange protocols secure in the standard model. The security analysis uses the powerful security model of Canetti and Krawczyk and a natural extension of it to the ID-based setting. It is shown how KEMs can be used in a generic way to obtain two different protocol designs with progressively stronger security guarantees. A detailed analysis of the performance of the protocols is included; surprisingly, when instantiated with specific KEM constructions, the resulting protocols are competitive with the best previous schemes that have proofs only in the random oracle model

Effect of feeding three lysine to energy diets on growth, body composition and age at puberty in replacement gilts

This study evaluated the effect of diets differing in standard ileal digestible (SID) lysine on lysine intake, growth rate, body composition and age at puberty on maternal line gilts. Crossbred Large White×Landrace gilts (n =641) were fed corn-soybean diets differing in SID lysine concentration (%, g SID lysine:Mcal ME); diets were not isocaloric. Gilts received three grower, finisher diet combinations: low (0.68% lysine grower, 0.52% lysine finisher), medium (0.79% lysine grower, 0.60% lysine finisher) or high (0.90% lysine grower, 0.68% lysine finisher). Grower diets were fed from 100 until 142 days of age, and finisher diets were fed until they reached 220 days of age. Body weight (BW), backfat thickness (BF), and loin depth (LD) were recorded every 28 days. From 160–220 days of age, gilts were exposed daily to vasectomized boars and observed for behavioral estrus. Gilts fed the low lysine diet had lower average daily gain and BW (P \u3c 0.05), but not fat depth:LD ratio. The percentage of gilts that displayed natural estrus by 220 days of age was low but not different among dietary treatments (low 27.7%, medium 31.0% and high 37.7%, respectively; P=0.1201). Gilts fed the high and medium diets reached puberty 10 and 6 days earlier, however, than gilts fed the low lysine diet (P \u3c 0.05). The rate of puberty attainment may have been less because all gilts contracted porcine epidemic diarrhea (PEDv) just as boar exposure was to begin for the first group of gilts. Results from the present study indicate that growth rate and age at puberty can be altered by ad libitum fed diets that differ in SID lysine concentration

ASICS: Authenticated Key Exchange Security Incorporating Certification Systems

Most security models for authenticated key exchange (AKE) do not explicitly model the associated certification system, which includes the certification authority (CA) and its behaviour. However, there are several well-known and realistic attacks on AKE protocols which exploit various forms of malicious key registration and which therefore lie outside the scope of these models. We provide the first systematic analysis of AKE security incorporating certification systems (ASICS). We define a family of security models that, in addition to allowing different sets of standard AKE adversary queries, also permit the adversary to register arbitrary bitstrings as keys. For this model family we prove generic results that enable the design and verification of protocols that achieve security even if some keys have been produced maliciously. Our approach is applicable to a wide range of models and protocols; as a concrete illustration of its power, we apply it to the CMQV protocol in the natural strengthening of the eCK model to the ASICS setting

Epitope Addition and Ablation via Manipulation of a Dengue Virus Serotype 1 Infectious Clone

ABSTRACT Despite the clinical relevance, dengue virus (DENV) research has been hampered by the absence of robust reverse genetic systems to manipulate the viral serotypes for propagation and generation of mutant viruses. In this article, we describe application of an infectious clone system for DENV serotype 1 (DENV1). Similar to previous clones in both flaviviruses and coronaviruses, the approach constructs a panel of contiguous cDNAs that span the DENV genome and can be systematically and directionally assembled to produce viable, full-length viruses. Comparison of the virus derived from the infectious clone with the original viral isolate reveals identical sequence, comparable endpoint titers, and similar focus staining. Both focus-forming assays and percent infection by flow cytometry revealed overlapping replication levels in two different cell types. Moreover, serotype-specific monoclonal antibodies (MAbs) bound similarly to infectious clone and the natural isolate. Using the clone, we were able to insert a DENV4 type-specific epitope recognized by primate MAb 5H2 into envelope (E) protein domain I (EDI) of DENV1 and recover a viable chimeric recombinant virus. The recombinant DENV1 virus was recognized and neutralized by the DENV4 type-specific 5H2 MAb. The introduction of the 5H2 epitope ablated two epitopes on DENV1 EDI recognized by human MAbs (1F4 and 14C10) that strongly neutralize DENV1. Together, the work demonstrates the utility of the infectious clone and provides a resource to rapidly manipulate the DENV1 serotype for generation of recombinant and mutant viruses. IMPORTANCE Dengue viruses (DENVs) are significant mosquito-transmitted pathogens that cause widespread infection and can lead to severe infection and complications. Here we further characterize a novel and robust DENV serotype 1 (DENV1) infectious clone system that can be used to support basic and applied research. We demonstrate how the system can be used to probe the antigenic relationships between strains by creating viable recombinant viruses that display or lack major antibody epitopes. The DENV1 clone system and recombinant viruses can be used to analyze existing vaccine immune responses and inform second-generation bivalent vaccine designs

Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study.

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 10(11) vp/mL, n = 21; 3 × 10(11) vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy

A Reverse Genetics Platform That Spans the Zika Virus Family Tree

ABSTRACT Zika virus (ZIKV), a mosquito-borne flavivirus discovered in 1947, has only recently caused large outbreaks and emerged as a significant human pathogen. In 2015, ZIKV was detected in Brazil, and the resulting epidemic has spread throughout the Western Hemisphere. Severe complications from ZIKV infection include neurological disorders such as Guillain-Barré syndrome in adults and a variety of fetal abnormalities, including microcephaly, blindness, placental insufficiency, and fetal demise. There is an urgent need for tools and reagents to study the pathogenesis of epidemic ZIKV and for testing vaccines and antivirals. Using a reverse genetics platform, we generated six ZIKV infectious clones and derivative viruses representing diverse temporal and geographic origins. These include three versions of MR766, the prototype 1947 strain (with and without a glycosylation site in the envelope protein), and H/PF/2013, a 2013 human isolate from French Polynesia representative of the virus introduced to Brazil. In the course of synthesizing a clone of a circulating Brazilian strain, phylogenetic studies identified two distinct ZIKV clades in Brazil. We reconstructed viable clones of strains SPH2015 and BeH819015, representing ancestral members of each clade. We assessed recombinant virus replication, binding to monoclonal antibodies, and virulence in mice. This panel of molecular clones and recombinant virus isolates will enable targeted studies of viral determinants of pathogenesis, adaptation, and evolution, as well as the rational attenuation of contemporary outbreak strains to facilitate the design of vaccines and therapeutics. IMPORTANCE Viral emergence is a poorly understood process as evidenced by the sudden emergence of Zika virus in Latin America and the Caribbean. Malleable reagents that both predate and span an expanding epidemic are key to understanding the virologic determinants that regulate pathogenesis and transmission. We have generated representative cDNA molecular clones and recombinant viruses that span the known ZIKV family tree, including early Brazilian isolates. Recombinant viruses replicated efficiently in cell culture and were pathogenic in immunodeficient mice, providing a genetic platform for rational vaccine and therapeutic design

Quantifying serum antibody in bird fanciers' hypersensitivity pneumonitis

BACKGROUND: Detecting serum antibody against inhaled antigens is an important diagnostic adjunct for hypersensitivity pneumonitis (HP). We sought to validate a quantitative fluorimetric assay testing serum from bird fanciers. METHODS: Antibody activity was assessed in bird fanciers and control subjects using various avian antigens and serological methods, and the titer was compared with symptoms of HP. RESULTS: IgG antibody against pigeon serum antigens, quantified by fluorimetry, provided a good discriminator of disease. Levels below 10 mg/L were insignificant, and increasing titers were associated with disease. The assay was unaffected by total IgG, autoantibodies and antibody to dietary hen's egg antigens. Antigens from pigeon serum seem sufficient to recognize immune sensitivity to most common pet avian species. Decreasing antibody titers confirmed antigen avoidance. CONCLUSION: Increasing antibody titer reflected the likelihood of HP, and decreasing titers confirmed antigen avoidance. Quantifying antibody was rapid and the increased sensitivity will improve the rate of false-negative reporting and obviate the need for invasive diagnostic procedures. Automated fluorimetry provides a method for the international standardization of HP serology thereby improving quality control and improving its suitability as a diagnostic adjunct